Acne is a group of diseases whose initial pathology is the comedo and includes acne vulgaris, neonatal acne, infantile acne, and pomade acne. There are approximately 45 million people who suffer from acne in America alone. The disease is so common in youth at their puberty that it often has been termed physiological. Although acne stops appearing for most people by the age of 25, some people, the majority of them are women, experience the disease well into their adult life. This “adult acne” differs from teenage acne in location and that it tends to be more inflammatory with fewer comedones. It has received a great deal of attention recently.
Acne is a chronic inflammatory disease affecting the sebaceous glands. Acne lesions primarily involve the sebaceous glands located on the face, neck, chest and back. Both closed comedones (blackheads) and open comedones (whiteheads) are caused by hyperkeratinization of the infundibulum of the sebaceous duct. These keritinous plugs block the flow of sebum. These dilated ducts abound with the colonies of Priopionibacterium acnes and other fat splitting organisms. The clinically evident open and closed comedones and the microscopic microcomedo are the signal lesions of acne. The acne process results from a cascade of events. First, at puberty a spike in androgen production heralds an increase in sebum production and begins the hyperkeratinization process causing microcomedones and sebum blockade. With this blockage, the number of resident follicular flora increases dramatically. These bacteria produce inflammatory products, which permeate through thin walls of dilated sebum-filled duct. Once in the perifollicular dermis, they trigger the body's own immune defenses (both acute and granulaomatous) to produce the characteristic inflammatory papules, pustules and nodules characteristic of inflammatory acne.
The term “acne” is used herein as a general term to include inflammatory diseases of the pilosebaceous unit. In the medical field, the specific type of acne is usually indicated by a modifying term, although the term acne is frequently used alone to designate common acne or acne vulgaris.
There are four factors that are generally believed to be the contributors to the development of acne, any of which evidence “an acne problem area”:    1. Increased sebum production;    2. Comedo formation, in which the follicular infundibulum hypercornifies, hyperkeratinizes, and hypodesquamates;    3. Colonization of the follicule by anaerobic Propionibacterium, mainly P. acnes; and    4. The host's inflammatory response.
These four factors are interrelated to each other. Sebum is comedogenic and causes inflammation by itself. The Propionibacterium has high lipolytic activity and liberates free fatty acids from sebum lipids. The free fatty acid has been shown to cause marked inflammation. The microorganisms also produce other extracellular enzymes such as proteases and hyaluronidases, and chemotactic factors, which may be important in the inflammatory process. Apart from these four factors, serum hormones, especially dehydroepiandrosterone sulfate, have been found to correlate with acne.
Acne commonly afflicts adolescents and young adults; however, there is growing number of patients who develop acne in their late twenties or thirties. There are data that suggest a familial or genetic tendency for patients to develop severe cystic or conglobate acne. Additionally, acne has been linked to endocrine disorders, especially those characterized by elevated levels of circulating testosterone or testosterone congeners. Exogenous agents that could exacerbate acne include medications e.g. iodides, anti-seisure, certain antibiotics and corticosteroids.
A number of dermatological disorders resemble acne having papules and pustules, but not comedones. These conditions represent follicular inflammation caused by drugs (androgens, lithium), bacteria, mechanical friction and unknown causes. Rosacea is the most common of these disorders and is receiving the most marketing attention with direct to consumer advertising by drug companies. This activity is directed toward the patients using topical metronidazole that appears to have anti-inflammatory activity. Treatment usually lasts 3 months.
Most acne treatments are directed at preventing inflammatory lesions, particularly the larger nodulo-cystic lesions that tend to be destructive and lead to permanent scarring. In general, visible comedones are the only minor cosmetic nuisances and do not lead to inflammatory lesions. Most acne treatment is directed to four arenas:    1. Keratinous plugs in sebaceous ducts;    2. Large sebaceous glands producing excess sebum;    3. Increased numbers of resident follicular bacteria; and    4. Inflammatory response to chemical mediators passing through the follicular wall.
Topical products used to remove comedones are known as comedolytics, the most effective being tretinoin, marketed as a prescription product (Retin A) and by several generic companies. Tretinoin or all-trans retinoic acid is the naturally occurring metabolite of Vitamin A. Tretinoin increases epidermal cell turnover, thus causing comedolysis and most importantly prevents the formation of new keratinous plugs. Applications of tretinoin is normally once a day at bedtime. Dryness, stinging and redness sometimes accompany the applications. Importantly, improvement is usually not seen for 6–8 weeks. Adapalene 0.1% (Differin) is a topical retinoid like tretinoin. Available by prescription only, the gel is usually applied once nightly. Side effects include frequent scaling, burning, redness and dryness. Improvement is delayed and is not evident for 4–8 weeks. Sodium sulfacetamide 10%/sulfur 5% (Sulfacet-R) is also available by prescription only. It is a lotion with antibacterial and comedolytic action. As with tretinoin, improvement is seen in 4–8 weeks. Salicylic acid 2% is an over the counter product that exhibits mild comedolytics activity.
The only products that have anti-sebum activity are estrogens and 13 cis-retinoic acid (isotretinoin) and these must be used systemically to be effective. Isotretinoin (Accutane) is a metabolite of Vitamin A available by prescription only. Isotretinoin is used to treat only severe cystic or conglobate acne. Because of its teratogenic properties, birth defects can occur. Isotretinoin is a powerful drug and can elevate triglycerides, total cholesterol and decrease high-density lipoproteins (HDL). Other side effects include dry skin, dry eyes, itching, headaches, nosebleed, and photosensitivity. It is generally taken for 4–5 months to see improvement. Recently, one brand of oral contraceptive has been approved for the treatment of acne for patients who request birth control.
A number of topical and systemic agents are used to lower the number of bacteria that colonize the follicular duct. These include benzoyl peroxide (BP), BP 5%/erythromycin 3% (Benzamycin). BP has antibacterial activity and drying effects and is available over the counter or by prescription. BP is applied once or twice daily for 1–2 months. BP can produce erythema and peeling of skin. BP is often tried first for both non-inflammatory and mild inflammatory acne. Other topical antibiotics include clindamycin and erythromycin. These are used as solutions, lotions or gels by prescription only. Usually they are applied once or twice daily and results are seen in 1–2 months. Azelaic acid 20% (Azelex) also has mild antibacterial effects.
Systemic antibiotics include tetracycline and its analogs, which are used in low doses for years or until the end of the acne prone years. Most patients with mild inflammatory acne receive a combination of topical antibiotics and tretinoin or other retinoid. Bacterial resistance does occur so antibiotics may be changed or BP is substituted since resistance does not occur with BP. More severe acne requires systemic antibiotics and topical retinoid. The most severe must receive oral isotretinoin for 4–5 months.
There are no drugs that directly affect the inflammatory acne. The retinoids do have some anti-inflammatory properties, but these are poorly described. Topical steroid and even systemic steroids have been used to abort a severe flare of fulminant acne, but these are limited uses because of the side effects. Benzoyl peroxide gels are sometimes used as first aid on acne lesions. These function as a “drawing poultice”, but data supporting this use is not available.
The treatment for acne centers around opening the pore, killing P. acnes, reducing sebum production and regulating inflammatory responses. Retinoids are the agents to reduce sebum production and open the pore. As a topical agent, Differin (adapalene) or Retin-A (tretinoin) is used for mild and moderate acne. Isotretinoin, an oral drug, is very effective but reserved for the severe and resistant acne because of its teratogenicity, hepatotoxicity, elevating triglyceride level and other side effects.
Topical and/or oral antimicrobial agents are commonly employed to treat acne. Topical benzoyl peroxide is used the most widely and is considered the best single topical agent. Tetracycline, Doxycycline and Minocycline are among the first line choices of oral antibiotics, in which Minocycline remains the premier drug for the treatment-resistant acne. Besides the side effects of the antimicrobial agents, development of resistant microorganisms has become an important issue nowadays. The number of patients harboring resistant P. acnes has been shown to be growing. While the patent literature reports that silver metal or silver salts such as silver nitrate, silver halides or silver sulphadiazine are amongst useful antibacterial agents for acne treatment, they have not, to the inventor's knowledge, been widely adopted for acne treatment.
Other approaches to acne include hormonal therapy with oral contraceptive pills as the major choice. It brings benefits to some patients over long term application. Intralesional corticosteroids and topical nicotinamide have also been used to control host's inflammatory response.